Development and validation of a nomogram model for predicting distant metastasis of aged ≥50 patients with thyroid carcinoma: a SEER database analysis.

OBJECTIVE: This work aimed to construct and validate a model for predicting distant metastasis (DM) in thyroid carcinoma (TC) patients aged≥50. PATIENTS AND METHODS: The research data were collected from the Surveillance, Epidemiology, and End Results (SEER) program databases via SEER*Stat software (https://seer.cancer.gov/). Logistics regression was used to screen the independent risk factors for TC patients. The nomogram was constructed and validated based on the logistics regression results for predicting DM occurrence in TC patients. Moreover, the characteristic curves (ROC) were used to assess the predictive performance. The decision analysis curve (DCA) and the calibration curve were used to test this nomogram's accuracy and discrimination. Additionally, we analyzed survival and risk scores in TC patients with metastasis using the Kaplan-Meier (KM) method. RESULTS: A total of 11,166 TC patients were divided into a training set and a validation set. The results showed that topography (T), lymph node metastasis (N), and (grade) G were crucial risk factors for predicting DM. ROC analysis showed that the model had a good discriminative ability both in the training and validation set. The DCA curve showed greater net benefits across a range of DM risks for the nomogram in the training and validation set. Survival analyses showed that the metastasis cases with low-risk scores have shown a poorer prognosis in this study, both in the training and validation set. CONCLUSIONS: The nomogram model had excellent predictive performance and net benefit for predicting DM of TC patients aged ≥50. The model can help doctors develop treatment plans for their patients.

Serum squamous cell carcinoma antigen level and magnetic resonance imaging for the prognosis of locally advanced cervical cancer.

OBJECTIVE: Squamous cell carcinoma antigen (SCC-ag) and magnetic resonance imaging (MRI) were explored to serve as biomarkers to predict the prognosis of cervical cancer (CC) patients treated with neoadjuvant chemotherapy (NACT) prior to radical surgery, with the aim of identifying the subgroup that least benefits from the combined therapy. PATIENTS AND METHODS: All patients were treated with NACT prior to radical surgery and received MRI and SCC-ag examinations before and after NACT. For these three cycles of NACT, patients were treated with intravenous paclitaxel at 150 mg/m2 over a period of 3 hours and carboplatin, with the area under the sera concentration-time curve of 5 over a period of 30 minutes on the first day of each cycle. Meanwhile, the blood pressure, ECG, and blood oxygen saturation of the patients were observed during the infusion. A discovery cohort and a validation cohort were applied to examine the prognostic performance of SCC-ag, MRI, and their combination. The endpoints of our study were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 384 patients diagnosed between August 2006 and December 2010 were enrolled in our research, with 206 patients in the discovery cohort and 178 patients in the validation cohort. The high-risk group identified by MRI had a worse OS [hazard ratio (HR), 3.567; 95% confidence interval (CI), 1.466-8.677; log-rank p=0.0027) and PFS (HR, 4.062; 95% CI, 2.171-7.6; log-rank p<0.0001) than the low-risk group. Meanwhile, the SCC-RC could serve as a strong prognostic factor to predict OS (HR, 5.614; 95% CI, 2.473-12.744; log-rank p<0.0001) and PFS (HR, 7.481; 95% CI, 4.194-13.344; log-rank p<0.0001) for CC. In addition, the combined MRI and SCC-ag had greater prognostic efficiency and were used to divide the whole patient population into three groups. Compared with patients in the low-risk group, patients in the high-risk group had a worse OS (HR, 8.216; 95% CI, 2.98-22.651; log-rank p<0.0001) and PFS (HR, 11.757; 95% CI, 5.735-24.104; log-rank p<0.0001). Multivariate analyses revealed that MRI, SCC-ag, and their combination were independent prognostic factors. CONCLUSIONS: SCC-ag and MRI, individually or in combination, were bound up with OS and PFS in CC. Additionally, the predictive efficiency improved when SCC-ag and MRI were combined in a risk model that predicted the OS and PFS of SCC compared with the predictive efficiency of either SCC-ag or MRI alone, revealing that the combination of these two biomarkers could help to ameliorate prognostic stratification and to guide personalized therapy for SCC patients.

[Endoscopic totally visceral sac separation for ventral hernias repair: anatomy notes and technical considerations].

The abdominal wall can be treated as a whole physiological and functional entity which is composed of multiple anatomical structures and planes. Surgical approaches and technical details that required are diverse in different area. Indeed, the abdominal wall is confined by several anatomical boundaries which make these surgical planes separated. If one could dissect these boundaries, then separated spaces could be connected, establishing an ample retromuscular/preperitoneal space to accommodate the mesh of ventral hernia repair. The concept of totally visceral sac separation (TVS) is achieved. The TVS concept is a summary of diverse ventral hernia repair techniques. Since its initiation and spread, this technique has been widely accepted and implemented by domestic surgeons due to its outstanding performance. This treatise will review the relevant anatomy as well assurgical tricks by the authors that aid in performing TVS. Some of the details are more tricky and harder to understand, thus this in-depth description of the technique.

[Comparative study of laparoscopic Keyhole and Sugarbaker technique in the treatment of terminal paracolostomy hernia].

Objective: To compare laparoscopic Keyhole repair with Sugarbaker repair in consecutive patients with parastomal hernia. Methods: From January 2015 to December 2021, 117 patients with parastomal hernia were treated with Keyhole or Sugarbaker laparoscopy repairs in the Department of Hernia and Bariatrci Surgery, the First Affiliated Hospital of University of Science and Technology of China, and the clinical data were retrospectively analyzed. There were 45 males and 72 females, aged (68.6±8.6) years (range: 44 to 84 years). Laparoscopic Sugarbaker repair was performed in 89 cases, and Keyhole repair was performed in 28 cases. The t-test, Mann-Whitney U test, χ2 test and Fisher exact test were used to compare the observation indicators between the two groups, such as operation time, incidence of operation-related complications, and postoperative recurrence rate. Results: The follow-up period was (M(IQR)) 33 (36) months (range: 12 to 84 months). Compared to the Sugarbaker group, the hernia ring area of the Keyhole group was bigger (35 (26) cm2 vs. 25 (16) cm2, Z=1.974, P=0.048), length of stay was longer ((22.0±8.0) d vs. (14.1±6.2) d, t=5.485, P<0.01), and the postoperative rate of recurrence was higher (28.6% (8/28) vs. 6.7% (6/89), χ2=7.675, P=0.006). There was no difference in operation time and postoperative complications between the two groups. Conclusions: Laparoscopic Sugarbaker repair is superior to Keyhole repair in the recurrence rate of parastomal hernia treated with compsite mesh (not funnel-shaped mesh). There are no differences in operation time and postoperative complications between the two groups.

Intracranial plaque characteristics on high-resolution MRI and high-sensitivity C-reactive protein levels: association and clinical relevance in acute cerebral infarction.

AIM: To investigate the association between intracranial plaque characteristics and high-sensitivity C-reactive protein (hs-CRP) levels, and their combined effects on the occurrence of acute cerebral infarction (ACI). MATERIALS AND METHODS: One hundred and forty-three patients with recent ischaemic events in the territory of middle cerebral artery or basilar artery were enrolled and divided into the ACI group (n=93) and non-ACI group (n=50) according to clinical data and diffusion-weighting imaging (DWI) results. All recruited patients underwent high-resolution magnetic resonance imaging (MRI) to assess intracranial plaque characteristics, including plaque enhancement, standardised wall index, stenosis ratio, T1 hyperintense component, remodelling pattern, plaque area, plaque burden, and maximum wall thickness. hs-CRP levels were further grouped into the low group (<1 mg/l), the intermediate group (1-3 mg/l), and the high group (≥3 mg/l). Multivariate logistic regression and receiver operating characteristic curve were constructed to evaluate the association between intracranial plaque characteristics and hs-CRP levels, as well as their synergistic effects on determining the occurrence of ACI. RESULTS: High hs-CRP levels were associated with strong plaque enhancement (p<0.001, odds ratio [OR] = 7.497). Strong plaque enhancement (p=0.002, OR=2.109) and high hs-CRP levels (p=0.009, OR=3.893) were independently associated with the occurrence of ACI after adjustments for sex, age, and other traditional atherosclerotic risk factors. The combination of hs-CRP levels and strong plaque enhancement provided incremental information to determine ACI with an AUC of 0.823, which was significantly higher than that of strong plaque enhancement (0.711) and hs-CRP levels (0.686), respectively. CONCLUSION: High hs-CRP levels were associated with strong plaque enhancement. The synergistic effects of hs-CRP levels and strong plaque enhancement provided incremental effects on the occurrence of ACI.

Assessment of the degree of arterial stenosis in intracranial atherosclerosis using 3D high-resolution MRI: comparison with time-of-flight MRA, contrast-enhanced MRA, and DSA.

AIM: To compare the accuracy of three-dimensional (3D) high-resolution (HR) magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography (TOF-MRA), contrast-enhanced magnetic resonance angiography (CE-MRA), and digital subtraction angiography (DSA) in measuring the degree of stenosis in intracranial atherosclerosis. MATERIALS AND METHODS: All patients with intracranial artery ischaemic events underwent HR-MRI, TOF-MRA, and CE-MRA analysis, and some of these patients underwent DSA examination. The correlation between different methods for measuring the degree of lumen stenosis was analysed. The accuracy of HR-MRI, TOF-MRA, and CE-MRA was evaluated and compared with that of DSA. RESULTS: A total of 189 arterial stenoses were identified in 93 patients. Of these, 72 patients with 142 arterial stenoses underwent DSA examination. A very strong correlation between HR-MRI and CE-MRA measurements was shown (r=0.839, p<0.0001). The correlation between HR-MRI and TOF-MRA measurements was strong (r=0.720, p<0.0001). A very strong correlation between HR-MRI and DSA measurements was found (r=0.864, p<0.0001), and a similar correlation was observed between CE-MRA, and DSA measurements (r=0.843, p<0.0001). The correlation between TOF-MRA and DSA measurements was strong (r=0.686, p<0.0001). There was substantial agreement between HR-MRI and DSA measurements (K = 0.772) and between CE-MRA, and DSA measurements (K = 0.734) that was slightly higher than the agreement between TOF-MRA and DSA measurements (K = 0.636). CONCLUSION: HR-MRI can accurately measure stenosis (especially for moderate and severe stenosis) in intracranial atherosclerosis by direct visualisation of the vessel lumen and steno-occlusive plaque.

[Analysis on individual dosage monitoring of some interventional radiology staffs in Tianjin City from 2016 to 2020].

Objective: To investigate the individual external dose level of some interventional radiology staffs from 2016 to 2020 in Tianjin City. Methods: All 2068 interventional radiology staffs who were included in the work of the Radiation Monitoring Project from 2016 to 2020 were selected as study subjects in March 2021. The individual dose monitoring results of interventional radiology staffs of different ages, working years, time and medical institutions were analyzed. Results: Among 2068 interventional radiology workers, 1406 (67.99%) were male and 662 (32.01%) were female. The age was 44.6 (39.2, 50.3) years, and the working years was 10.5 (4.3, 14.6) years. The annual effective doses per capita of 40-49 age group and ≥50 age group were higher than that of 30-39 age group (P<0.05) . The annual effective dose per capita of 5-9 working years was higher than that of <5 working years, and the annual effective dose per capita of 10-29 working years was higher than that of 5-9 working years (P<0.05) . The median per capita annual effective dose of the interventional radiology staffs was 0.164 mSv. There were 1976 interventional radiology staffs with an annual effective dose of <0.50 mSv/a (95.6%) . The collective dose distribution ration SR(0.5) was 41.1%. The difference of effective dose per capita in each year was statistically significant (H=19.23, P<0.05) . The per capita annual effective dose of interventional radiology staffs in tertiary medical institutions was higher than that in secondary medical institutions, and the difference was statistically significant (P<0.05) . Conclusion: The personal dose of interventional radiology staffs in Tianjin City is at a low level. It is necessary to emphasize the radiation hazard protection of interventional radiology staffs in tertiary medical institutions, 40-49 years old, ≥50 years old age groups and 5-9, 10-29 working years groups.

[Current status of hyperkalemia in dialysis patients in China].

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

[Effects of occupational stress and related factors on insomnia occurrence of workers in chip manufacturing industry].

Objective: To investigate the prevenlence of insomnia on workers and related influcecing factors in chip manufacturing industry. Methods: By using cluster sampling method, 2 251 workers in chip manufacturing industry were selected as study subjects. The simple Job Demand-Control model Questionnnaire (JDC) , Effort-Reword Imbalance (ERI) Questionnnaire and Insomnia Symptoms Scale were used to evaluate JDC occupational stress, ERI occupational stress and insomnia symptoms respectively. Results: 22.6% (509/2251) workers were found high level of insomnia. The risk factors of insomnia symptoms were high score of effort and overcommitment (P< 0.05) . The risk of insomnia symptoms in high effort was 1.689 times that of low score (95%CI: 1.334-2.138) . The risk of insomnia symptoms in high overcommitment was 1.835 times that of low score (95%CI: 1.461-2.305) . The protective factors for insomnia symptoms were women, monthly income of more than 3000 yuan, college dregree or above, high work control and high reward (P<0.05) . Conclusion: The high scores of effort and overcommitment are the risk factors for insomnia symptoms of employees in manufacture electronic devices. Enterprises should take comprehensive measures to pay attention to the occurrence of insomnia symptoms among employees with high score of effort and overcommitment.

[Diagnosis and treatment of basal cell adenoma of parotid gland].

Objective:To investigate the clinical features, diagnosis and treatment experience of basal cell adenoma (BCA).Method:The clinical data of 7 patients with basal cell adenoma of the parotid gland from the Second Affiliated Hospital of Medical University of Anhui from March 2012 to June 2016 were retrospectively analyzed. Combined with literature review, the experience of diagnosis and treatment was discussed.Result:Seven BCA were mostly diagnosed as pleomorphic adenoma and adenomatous lymphoma before operation using parotid ultrasound, fine needle aspiration cytology and parotid enhanced CT, and no patients was diagnosed as BCA prior to the operation. Four cases were diagnosed as BCA, 1 case was diagnosed as adenoma, 1 case was diagnosed as low-grade malignant tumor, and 1 case was not able to identify benign or malignant tumor by intraoperative fast frozen pathological examination. There were no obvious complications after the operation, and only 2 cases of mild facial paralysis returned to normal in 1 month, and no recurrence was found in the follow-up 18-69 months. Conclusion:Basal cell adenoma of the parotid gland is a rare benign tumor of parotid gland, the lack of specific clinical manifestations and signs, preoperative ultrasonography, fine needle aspiration cytology and parotid gland enhanced CT scan can not confirm the diagnosis, although they have some limitations, they are of great value in the localization, qualitative and differential diagnosis of BCA in the parotid gland. The diagnosis mainly depends on intraoperative, postoperative pathology and immunohistochemical examination. The treatment is mainly surgical excision, and the prognosis is better.

Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: A vicious cycle.

Inflammasomes are caspase-1-activating molecular platforms that produce active interleukin (IL)-1ß and are implicated in various central nervous system (CNS) diseases. These multi-protein complexes can be activated by exposure of cells to low osmolality. The inflammasome nucleotide-binding and oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) is hereby the main sensor of cellular osmolality. IL-1ß was found to stimulate the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland either by action of prostaglandins or indirectly by causing the release of IL-6. Based on these findings, we hypothesize that the hyponatremia caused by a wide range of CNS diseases is able to induce significant cell swelling with induction of a hyposmotic intracellular environment, which activates the NLRP3 inflammasome, causing the release of IL-1ß and induced by IL-1ß, IL-6, which increases the production of ADH that leads to more profound hyponatremia. Supportive evidence for this hypothesis is the finding that IL-1 injection can induce ADH release and hyposmotic effect of ADH induced hyponatremia can, via the mechanical effect of cell swelling, activate transient receptor potential channels, which via transforming growth factor ß-activated kinase 1 activate NLRP3. Implications of this hypothesis, if confirmed, would include that hyponatremia can be exacerbated through this vicious cycle but also that the inflammasomes are key mediators of this process. Confirmation of this hypothesis would have implications for prevention and clinical management of changes in patients sodium levels related to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with interventions targeting inflammatory mediator production and function of inflammasomes with the potential of prevention of permanent brain damage in a wide range of CNS diseases.

Genes and pathways identified in thyroid carcinoma based on bioinformatics analysis.

The objective of this study was to investigate the key genes and pathways associated with thyroid carcinoma. Based on the microarray data of GSE27155, we identified the differentially expressed genes (DEGs) between four types of thyroid carcinoma samples (papillary carcinoma (PTC), oncocytic carcinoma (OTC), follicular carcinoma (FTC) and anaplastic carcinoma (ATC)) and normal controls. With the obtained DEGs, we performed gene functional interaction (FI) network analysis. Then we conducted Venn diagram analysis to identify the intersection and specific DEGs of the four types of thyroid carcinomas. The intersections DEGs were performed by functional enrichment and transcription factor (TF) prediction analyses. These specific DEGs were performed by pathway enrichment analysis. There were respectively 323, 318, 118 and 1005 DEGs identified in PTC, OTC, FTC and ATC. Twelve sub-network modules were extracted based on gene FI network analysis and eight thyroid carcinoma-associated DEGs were involved in the network, such as TIMP1. Based on the Venn diagram analysis, 27 common DEGs were identified, such as HMGB3 which was regulated by TF of NKX3-1. There were 149 PTC-specific DEGs (like CLDN1), 160 OTC-specific DEGs, 94 FTC-specific DEGs (like PPARG), and 789 ATC-specific DEGs (like CDK1). They were enriched in some pathways, such as Cell cycle, Citrate cycle, and Oxidative phosphorylation. TIMP1, HMGB3, CLDN1, CDK1 and PPARG as well as pathways of Cell cycle, Citrate cycle, and Oxidative phosphorylation may play important roles in the progression of thyroid carcinoma.

High-resolution anorectal manometry in newborns: normative values and diagnostic utility in Hirschsprung disease.

BACKGROUND: Conventional methods of screening for Hirschsprung disease (HD) in newborns (barium enema, BE; anorectal manometry, ARM; rectal suction biopsy, RSB) have limitations and/or are invasive. High-resolution anorectal manometry (HR-ARM) is a minimally invasive technique that has potential to overcome most of these limitations, but normative data and performance characteristics have not been reported in newborns. The aims of our study were to assess anorectal sphincter metrics including resting pressure (RP), anal canal length (ACL), and rectoanal inhibitory reflex (RAIR) in healthy and asymptomatic newborns, and to explore the role of HR-ARM in the diagnosis of HD using these normal parameters. METHODS: All procedures were performed using solid state HR-ARM equipment (Medical Measurement Systems, Enchede, The Netherland) by a single operator. In the first phase, 180 asymptomatic newborns (term newborns 95, preterm newborns 85) were studied, and anal RP, ACL, and RAIR were measured. In the second phase, 16 newborns with clinical manifestations of HD were studied (9 of whom had histopathologic confirmation), and parameters compared to asymptomatic newborns. KEY RESULTS: Normative RP values were higher in term newborns compared with preterm newborns (p < 0.05), and correlated with age. Progressive maturation of the anal sphincter was evident with chronologic age, both in preterm and term newborns. RAIR was present in all normal subjects. Using absent RAIR as indicative of HD, HR-ARM had a sensitivity 89% and specificity of 83% compared to RSB; these performance characteristics were better than BE (sensitivity 78%, specificity 17%), with significantly higher diagnostic accuracy (80% vs 53%, respectively, p = 0.009). CONCLUSIONS & INFERENCES: Anorectal sphincter pressure progressively matures with incremental increase in RP during the first months of life. HR-ARM is an effective and safe method that complements the diagnosis of HD in newborns.

Flow pattern analysis of a full-scale expanded granular sludge bed-type reactor under different organic loading rates.

The hydraulic characteristics of a lab-scale and a full-scale (275 m(3)) expanded granular sludge bed (EGSB)-type reactor under different organic loading rates varying from 10 kg COD m(-3)d(-1) to 45 kg COD m(-3)d(-1) were investigated. A modified combined model composed of two completely mixing regions and a plug flow region was sufficient for simulating the flow pattern of a full-scale EGSB-type reactor. Moreover, the outputs fitted the measured tracer distribution results well. The simplified model structure was in very good agreement with the physical structure of a full-scale EGSB-type reactor. The upflow (liquid+gas) velocity, high concentration of granular sludge, and gas hold-up effect may contribute to the generation of dead spaces (maximum of 19.5%). The bed expansion characteristics indicated that the sludge bed of the EGSB-type reactor performed as a suspended bed, in which the bed expansion was controlled between 20% and 30%, rather than the usually considered expanded bed.

FLIP and the death effector domain family.

Death effector domains (DEDs) are protein interaction modules found in a number of proteins known to regulate apoptosis from death receptors. The core DED family members that orchestrate programmed cell death from death receptors include the adaptor protein FADD, the initiator caspases procaspases-8 and -10 and the regulatory protein c-FLIP. Through homotypic DED interactions, these proteins assemble into the death-inducing signaling complex (DISC) to regulate initiator caspase activation and launch the apoptotic proteolytic cascade. A considerable body of evidence, however, is revealing that the same core group of DED-containing proteins also paradoxically promotes survival and proliferation in lymphocytes and possibly other cell types. This review delves into recent findings regarding these two opposing functional aspects of the core DED proteins. We discuss the current effort expanding our structural and biochemical view of how DED proteins assemble into the DISC to fully activate initiator caspases and execute cell death, and finally we examine details linking the same proteins to proliferation and describe how this outcome might be achieved through restricted activation of initiator caspases.

Mutations in NALP12 cause hereditary periodic fever syndromes.

NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-kappaB signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means.

The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation.

Pyroptosis is a caspase-1-dependent inflammatory form of cell death. The adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli. To elucidate the mechanism of activation of caspase-1 by ASC and its exact role in macrophage pyroptosis, we performed time-lapse confocal bioimaging analysis on human THP-1 macrophages stably expressing an ASC-GFP fusion protein. We show that stimulation of these cells with several proinflammatory stimuli trigger the formation of a large supramolecular assembly of ASC, termed here pyroptosome. Only one distinct pyroptosome in each stimulated cell is formed, which rapidly recruits and activates caspase-1 resulting in pyroptosis and the release of the intracellular proinflammatory cytokines. The pyroptosome is largely composed of oligomerized ASC dimers. Dimerization of ASC is driven by subphysiological concentrations of potassium as in vitro incubation of purified recombinant ASC in the presence of subphysiological concentrations of potassium induces the assembly of a functional pyroptosome. Furthermore, stimulation of potassium efflux in THP-1 cells with potassium-depleting agents induces formation of the pyroptosome, while increasing potassium concentrations in the culture medium or pharmacological inhibition of this efflux inhibits its assembly. Our results establish that macrophage pyroptosis is mediated by a unique pyroptosome, distinct from the inflammasome.

Acousto-optic polarization-dependent mode coupling in a dual-mode hollow optical fiber.

We demonstrated unique polarization dependence in acousto-optic coupling in a two-mode hollow optical fiber (HOF). Local deformation of circular HOF induced by traveling acoustic wave resulted in highly birefringent optical transmission characteristics, which were experimentally analyzed for various central air-hole sizes. Potential applications for polarization-dependent devices such as polarization-dependent loss compensators and broadband polarization controllers are discussed.

Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization.

Mutations in cryopyrin and pyrin proteins are responsible for several autoinflammatory disorders in humans, suggesting that these proteins play important roles in regulating inflammation. Using a HEK293 cell-based reconstitution system that stably expresses ASC and procaspase-1 we demonstrated that neither cryopyrin nor pyrin or their corresponding disease-associated mutants could significantly activate NF-kappaB in this system. However, both cryopyrin and two disease-associated cryopyrin mutants induced ASC oligomerization and ASC-dependent caspase-1 activation, with the disease-associated mutants being more potent than the wild-type (WT) cryopyrin, because of increased self-oligomerization. Contrary to the proposed anti-inflammatory activity of WT pyrin, our results demonstrated that pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, caspase-1 activation and interleukin-1beta processing. Thus, we propose that pyrin could function as a proinflammatory molecule.